DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) The cytokine transforming growth factor beta-1 (TGF-b1) has been implicated in the pathogenesis of certain lung diseases associated with pulmonary vascular injury and remodeling. However, its mechanism of action on cells is not known. The application hypothesizes that TGF-b1 may affect the pulmonary vasculature and possibly other components of the lung through alterations in oxidant/anti-oxidant systems within lung cells. The Specific Aims are to: 1) evaluate the mechanism of the "pro- oxidant" effect of TGF-b1 on endothelial cells; 2) determine the mechanism by which TGF-b1 reduces cellular glutathione; 3) better define the regulatory role of TGF-b1 on cellular Cu, Zn- and Mn-SOD; and 4) evaluate the concept that TGF-b1 perpetuates its oxidant/anti-oxidant effects on endothelial cells through an autocrine action that is regulated by the cellular glutathione content. The studies may provide new insights into the actions of TGF-b1 on pulmonary vascular endothelial cells, in particular, and may provide a broader interpretation of the action of TGF-b1 on cells in general. They may also help to better understand at the cellular level the pathogenesis of certain lung diseases characterized by tissue injury and remodeling, thereby leading to new therapeutic options.